1. Field of the Invention
This invention relates to novel 3-(4-cyano-4-phenylalkyl)tetrahydroisoquinoline derivatives and the pharmaceutically acceptable salts thereof, pharmaceutical compositions containing said derivatives or salts, and the use thereof to treat cardiovascular disorders including angina, hypertension, and congestive heart disease. This invention also relates to a novel process for preparing the compounds of the invention, and novel intermediates therefor.
2. Related Disclosure
Certain other calcium channel blocking agents are known, such as verapamil, N-[4-(3,4-dimethoxyphenyl)-4-cyano-4-(prop-2-yl)butyl]-N-(3,4-dimethoxyphe nethyl)-N-methylamine, (U.S. Pat. No. 3,261,859). Although verapamil has enjoyed widespread commercial success, it is short-acting, necessitating administration three or four times per day. Also, it is cardiodepressive, and decreases cardiac conduction. It has now been found that the compounds of the invention are less cardiodepressive and longer-acting than verapamil. Compounds of the invention are orally active and decrease afterload and preload, while increasing coronary bloodflow. Compounds of the invention also increase the heart rate pressure product without increasing the heart rate. Compounds of the invention do not cause pathological prolongation of A-V conduction at effective concentrations, and do not cause orthostatic hypotension. Compounds of the invention decrease ECG ST-segment elevation in pacing-induced angina models.